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Determination of dexmedetomidine using high performance liquid chromatography coupled with tandem mass spectrometric (HPLC-MS/MS) assay combined with microdialysis technique: Application to a pharmacokinetic study.
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2020-09-08 , DOI: 10.1016/j.jchromb.2020.122381
Pan Chang 1 , YuJun Zhang 1 , DeYing Gong 2 , LingHui Yang 2 , Jing Wang 2 , Jin Liu 1 , WenSheng Zhang 1
Affiliation  

Dexmedetomidine, as a safe sedative, mainly exerts on the central nervous system particularly in the locus coeruleus producing arousable sedation with potential analgesic and anxiolytic effects. The quantification and pharmacokinetic investigation of dexmedetomidine in the central nervous system have been described rarely. In order to estimate the unbound dexmedetomidine concentrations in brain extracellular fluid and blood simultaneously, we employed microdialysis technique as a sampling method and primarily established a rapid, sensitive and selective high-performance liquid chromatography coupled with tandem mass spectrometry method (HPLC-MS/MS). Dexmedetomidine and the internal standard (dexmedetomidine-d4) were extracted in liquid–liquid extraction procedure with ethyl acetate from 10 μL of alkalinized microdialysate sample. After evaporation under nitrogen at room temperature, the analytes were reconstituted in acetonitrile and transferred to be detected. HPLC was performed on an Agilent Poroshell 120 Hilic column (4.6 × 100 mm, 2.7 μm) with isocratic elution at a flow rate of 0.3 mL/min by 0.1% formic acid/acetonitrile (60:40, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring (MRM) mode using the respective [M+H]+ ions m/z 201.2 to m/z 95.1 for DEX and m/z 205.2 to m/z 99.1 for IS (DEX-d4). The concentration–response relationship was of good linearity over a concentration range of 1.00–1000.00 ng/mL with the correlation coefficient above 0.999. The lower limit of quantification was 1.00 ng/mL with a relative standard deviation of less than 20%. The intra- and inter-day accuracy were within ±5.00% and precision was <7.23%. The recoveries of dexmedetomidine in microdialysates were 76.61–93.38%. The validated HPLC-MS/MS method has been successfully applied to study the pharmacokinetics of dexmedetomidine in rats after a caudal vein administration.



中文翻译:

高效液相色谱-串联质谱法(HPLC-MS / MS)结合微透析技术测定右美托咪定:在药代动力学研究中的应用。

右美托咪定作为一种安全的镇静剂,主要作用于中枢神经系统,尤其是在蓝斑中,产生可唤醒的镇静作用,具有潜在的镇痛和抗焦虑作用。很少描述右美托咪定在中枢神经系统中的定量和药代动力学研究。为了同时估算脑细胞外液和血液中未结合的右美托咪定的浓度,我们采用微透析技术作为采样方法,并初步建立了快速,灵敏和选择性的高效液相色谱-串联质谱法(HPLC-MS / MS )。右旋美托咪定和内标(dexmedetomidine-d4)在液-液萃取过程中用乙酸乙酯从10μL碱化微透析液样品中萃取。在室温下在氮气下蒸发后,分析物在乙腈中重构并转移以进行检测。HPLC在Agilent Poroshell 120 Hilic色谱柱(4.6×100 mm,2.7μm)上进行等度洗脱,流速为0.3 mL / min,用0.1%甲酸/乙腈(60:40,v / v)。在多反应监测(MRM)模式下在三重四极杆串联质谱仪上进行检测,分别使用DE的[M + H] +离子m / z 201.2至m / z 95.1和m / z 205.2至m / zIS(DEX-d4)为99.1。浓度-响应关系在1.00-1000.00 ng / mL的浓度范围内具有良好的线性关系,相关系数高于0.999。定量下限为1.00 ng / mL,相对标准偏差小于20%。日内和日间准确度在±5.00%以内,精确度<7.23%。微量透析液中右美托咪定的回收率为76.61–93.38%。经验证的HPLC-MS / MS方法已成功地用于研究右美托咪定在大鼠尾静脉给药后在大鼠体内的药代动力学。

更新日期:2020-09-16
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